文献类型：期刊文献

英文题名：Process optimization with alternative carbon sources and modulation of secondary metabolism for enhanced ansamitocin P-3 production in Actinosynnema pretiosum

作者：Fan, Yuxiang[1];Gao, Yang[1];Zhou, Jie[1];Wei, Liujing[1];Chen, Jun[1];Hua, Qiang[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]SCICBT, Shanghai 200237, Peoples R China

年份：2014

卷号：192

期号：Part A

起止页码：1

外文期刊名：JOURNAL OF BIOTECHNOLOGY

收录：;EI(收录号：20144600209939);WOS:【SCI-EXPANDED(收录号:WOS:000345970300001)】；

基金：This work was financially supported by the National Basic Research Program of China (973 Program) (2012CB721101), Research Fund for the Doctoral Program of Higher Education of China (20130074110002), National Natural Science Foundation of China (21406070). We are grateful to Prof. Lin-Quan Bai, Prof. Jian-Jiang Zhong and Dr. Qian-Jin Kang at Shanghai Jiao Tong University, China, for their valuable advices.

语种：英文

外文关键词：Actinosynnema pretiosum; Ansamitocin P-3; Fructose; Medium optimization; Transcription analysis

摘要：Ansamitocin P-3 (AP-3), synthesized by Actinosynnema pretiosum, is a microtubule disruptor with significant antitumor activity. Although efforts have been made for the study of ansamitocin biosynthetic gene clusters and its fermentation improvement, the yield and productivity of AP-3 are still limited. In this study, fructose was found to be more beneficial to AP-3 production than glucose, and the culture condition was optimized via single-factor experiments and response surface method. The AP-3 concentration in the Erlenmeyer flasks reached 144 mg/L with the optimized medium containing fructose 9.36 g/L, glycerol 26.79 g/L and soluble starch 3.03 g/L, increased by ninefold compared with that before optimization. The result of medium optimization showed that fructose was an important element for effective increase in AP3 production. Transcription of genes involved in primary metabolism and ansamitocin biosynthetic pathway was investigated to elucidate metabolic responses of cell metabolism to the substitution of fructose for glucose. It was demonstrated that using fructose as the major carbon source could relieve glucose repression and therefore result in flux rearrangement in primary metabolism for better providing biosynthetic precursors and stimulating the secondary metabolism in A. pretiosum. The results obtained might be of particular benefit to further enhancement of ansamitocin productivity. (C) 2014 Elsevier B.V. All rights reserved.